Various tissues and cultured cell lines are being examined as potential sources of nerve growth factor. Nerve growth factor-like activity from novel tissue sources and from cultured cells are being purified and characterized to determine what structural relationship they bear to mouse 7S NGF. In particular, nerve growth factor-like activity, assayed on chick embryo sensory neurons, is being purified from chick embryo iris, and from mouse L cells. In addition, the mechanism of action of nerve growth factor is being investigated using pheochromocytoma PC12 cells as a model system. Clonal mutants of PC12 cells which are defective in response to nerve growth factor have been isolated and are being phenotypically characterized and genetically characterized by analysis of complementation between mutants using cell hybridization techniques.